Background Clinical practice guidelines (CPG) are useful tools to help patients, health professionals, and policymakers to make evidence-based decisions about health care; consequently, they need to be updated in order to guarantee the validity of recommendations. Objectives The main objectives of this thesis are: 1) to identify and describe the methods used to update CPGs and 2) to design and evaluate new methods for updating CPGs. Methodology We conducted five studies with different methodologies: 1) an international survey on CPG updating process; 2) a systematic review of CPG updating methods; 3) a survival analysis to estimate the length of time before recommendations become outdated; 4) an assessment of updated recommendations, and 5) an evaluation of two pragmatic search strategies to identify the need to update recommendations. Results In the international survey, 92. 0% of the institutions (36/39) report the update of their guidelines. The 52. 8% (19/36) have a formal procedure for deciding when a guideline becomes out of date. The 86. 1% (31/36) have a formal procedure for updating their guidelines; nevertheless, only 25% (9/36) piloted such process. In the systematic review, we included a total of eight studies: four studies evaluated whether CPGs were out of date; three studies were actually CPG updates; and in one study CPGs were continuously monitored and updated. The most detailed reported phase of the process was the identification of new evidence. One study compared a restricted versus an exhaustive search, suggesting that a restricted search is sufficient to assess the validity of recommendations. Another study analysed the survival time of CPGs and suggested that these should be reassessed every three years. In the recommendations survival analysis (113 recommendations included in four guidelines from the Spanish National Health System's CPG Programme), 92. 0% of the recommendations were valid one year after their development (95% confidence interval: 86. 9 to 97. 0). This probability gradually decreased (85. 7%, 81. 3%, 77. 8% at two, three and four years, respectively). In the updated recommendations assessment (1306 recommendations produced by the National Institute for Health and Care Excellence), presentation formats used to indicate the changes in recommendations varied widely across CPGs. The majority of these changes were not explained. We did not perform an analysis to identify potential predictive factors for updating, given the small sample of recommendations retrieved. In the assessment of pragmatic search strategies, the restrictive search retrieved 68. 1% fewer references than those retrieved by the exhaustive search (12,486 versus 39,136), and identified 89. 9% (62/69) of key references. The use of McMaster PLUS database retrieved 88. 5% fewer references than those retrieved by the exhaustive search (4,486 versus 39,136), but identified substantially fewer key references (18/69, 26. 1%). Conclusions Institutions involved in developing CPGs do not have a standardised CPG updating process. Furthermore, there is very limited methodological research into the CPG updating process, with available research focusing mainly on evidence search strategy. Recommendations swiftly become outdated. A restrictive and continuous search strategy, prioritizing clinical questions with a higher rate of scientific production, could be an efficient and feasible method to identify studies that signal for updating CPGs. Methodological research must be continued in order to improve and standardise the CPGs updating process, and to implement and assess the results of this research in CPG programmes.